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A correction has been published: N Engl J Med 1997;336(9):670.

Previous Volume 335:1261-1267 October 24, 1996 Number 17 Next

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ABSTRACT

Background Kaposi's sarcoma is the most common cancer in patients with the acquired immunodeficiency syndrome (AIDS). Recently, certain preparations of human chorionic gonadotropin (hCG) have been shown to inhibit the growth of Kaposi's sarcoma cell lines in vitro and in immunodeficient mice.

Methods After in vitro evaluation of four commercially available hCG preparations, the most active product was evaluated in 36 patients with AIDS-related Kaposi's sarcoma. In a phase 1–2 trial, 24 patients received intralesional injections of hCG three times a week for two weeks at doses of 250, 500, 1000, or 2000 IU (6 patients each). In each patient three nodular lesions were injected, two with the drug and one with diluent alone. In a double-blind trial, 12 additional patients were randomly assigned to receive intralesional injections of 2000 IU of hCG or diluent alone (6 patients each; two lesions per patient). At the conclusion of therapy, the lesions were measured, their gross appearance assessed, and biopsy specimens evaluated.

Results A.P.L. (Wyeth–Ayerst), which had the most in vitro activity against Kaposi's sarcoma cell lines, was selected for the clinical investigation. Treatment with A.P.L. was well tolerated at all doses. In the cohorts given 250, 500, 1000, and 2000 IU, 1, 5, 5, and 10 of the 12 injected lesions responded, respectively (P = 0.03 for trend). Complete tumor regression was observed in one lesion each at the 250-IU and 500-IU doses, in two lesions given the 1000-IU dose, and in five lesions given the 2000-IU dose. In the double-blind study, none of the 12 lesions in the six patients injected with diluent had responses, as compared with 10 of the 12 lesions in the six patients injected with hCG (P = 0.015). Microscopical evidence of apoptosis was observed only in hCG-treated lesions. The percentage of cells that died increased in a dose-dependent manner (P<0.001). Serum levels of follicle-stimulating hormone (P = 0.002) and luteinizing hormone (P = 0.001) declined after the last injection of hCG, but there was no effect on these hormones in the diluent-treated patients.

Conclusions The intralesional injection of hCG induces the regression of AIDS-related Kaposi's sarcoma lesions in a dose-dependent manner. The response of these tumors appears to be mediated by the induction of apoptosis.

Source Information

From the Departments of Internal Medicine (P.S.G., A.T., T.Z., B.M.E., A.M.L.) and Pharmacy (S.L.), University of Southern California School of Medicine, Los Angeles; the Institute of Human Virology, University of Maryland, Baltimore (Y.L.-I., J.L.B., R.C.G.); the Department of Infectious Diseases, St. Pierre Hospital, Université Libre de Bruxelles, Brussels, Belgium (P.H.); and the Gynecology and Obstetrical Medical Center, Paris (J.M.B.).

Address reprint requests to Dr. Gill at the University of Southern California, Norris Cancer Hospital and Research Institute, 1441 Eastlake Ave., Rm. 162, Los Angeles, CA 90033.

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Intralesional Human Chorionic Gonadotropin for Kaposi's Sarcoma
Harris P. J., Russo I. H., Grulich A. E., Kaldor J. M., Gill P. S., Lunardi-Iskandar Y., Gallo R. C., Krown S. E., Rabkin C. S.
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N Engl J Med 1997; 336:1187-1189, Apr 17, 1997. Correspondence

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